title: Attenuation of systemic morphine-induced analgesia by central administration of ghrelin and related peptides in mice.
abstract: Ghrelin, an acylated 28-amino peptide secreted in the gastric endocrine cells, has been demonstrated to stimulate the release of growth hormone, increase food intake, and inhibit pro-inflammatory cascade, etc. Ghrelin mainly combines with its receptor (GHS-R1α) to play the role in physiological and pathological functions. It has been reported that ghrelin plays important roles in the control of pain through interaction with the opioid system in inflammatory pain and acute pain. However, very few studies show the effect of supraspinal ghrelin system on antinociception induced by intraperitoneal (i.p.) administration of morphine. In the present study, intracerebroventricular (i.c.v.) injection of ghrelin (0.1, 1, 10 and 100 nmol/L) produced inhibition of systemic morphine (6 mg/kg, i.p.) analgesia in the tail withdrawal test. Similarly, i.c.v. injection GHRP-6 and GHRP-2 which are the agonists of GHS-R1α, also decreased analgesia effect induced by morphine injected intraperitoneally in mice. Furthermore, these anti-opioid activities of ghrelin and related peptides were not blocked by pretreatment with the GHS-R1α selective antagonist [d-Lys(3)]-GHRP-6 (100 nmol/L, i.c.v.). These results demonstrated that central ghrelin and related peptides could inhibit the analgesia effect induced by intraperitoneal (i.p.) administration of morphine. The anti-opioid effects of ghrelin and related peptides do not interact with GHS-R1a. These findings may pave the way for a new strategy on investigating the interaction between ghrelin system and opioids on pain modulation.
authors.affiliation: Department of Physiology, Medical College of Nanchang University, Bayi Road 461, Nanchang, Jiangxi 330006, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.forename: Jia-Xiang
authors.initials: JX
authors.lastname: Chen
authors.forename: Bei
authors.initials: B
authors.lastname: Yang
authors.forename: Xing
authors.initials: X
authors.lastname: Zhi
authors.forename: Fa-Xian
authors.initials: FX
authors.lastname: Guo
authors.forename: Meng-Li
authors.initials: ML
authors.lastname: Sun
authors.forename: Jing-Lei
authors.initials: JL
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Wei
mesh_terms: D000698:Analgesia / Q000523:psychology*; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D000818:Animals; D054439:Ghrelin / Q000008:administration & dosage*; D006358:Hot Temperature; D007274:Injections, Intraperitoneal; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage* / Q000037:antagonists & inhibitors; D059225:Nociception / Q000187:drug effects* / Q000502:physiology; D009842:Oligopeptides / Q000008:administration & dosage; D054440:Receptors, Ghrelin / Q000819:agonists / Q000378:metabolism; D013623:Tail / Q000502:physiology
chemical_list: D000701:Analgesics, Opioid; C520836:GHRP-6, Lys(3)-; D054439:Ghrelin; D009842:Oligopeptides; D054440:Receptors, Ghrelin; C041048:growth hormone releasing hexapeptide; D009020:Morphine; C091874:growth hormone-releasing peptide-2
keywords: GHRP-2; GHRP-6; Ghrelin; Morphine; Tail withdrawal test; [d-Lys(3)]-GHRP-6